A Study Of PF-05082566 As A Single Agent And In Combination With Rituximab
A PHASE 1 STUDY OF PF-05082566 AS A SINGLE AGENT IN PATIENTS WITH ADVANCED CANCER, AND IN COMBINATION WITH RITUXIMAB IN PATIENTS WITH NON-HODGKIN'S LYMPHOMA (NHL)
2 other identifiers
interventional
190
5 countries
42
Brief Summary
A study of PF-05082566, a 4-1BB agonist monoclonal antibody (mAb), in patients with solid tumors or b-cell lymphomas, and in combination with rituximab in patients with CD20 positive Non-Hodgkin's Lymphoma (NHL).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jun 2011
Longer than P75 for phase_1
42 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 28, 2011
CompletedFirst Posted
Study publicly available on registry
March 2, 2011
CompletedStudy Start
First participant enrolled
June 21, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 20, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
February 20, 2019
CompletedResults Posted
Study results publicly available
March 17, 2020
CompletedMarch 17, 2020
March 1, 2020
7.7 years
February 28, 2011
January 31, 2020
March 4, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Number of Participants With Dose-Limiting Toxicities (DLTs) in First 2 Cycles of Portion A
DLT: Any of the following adverse events (AEs) occurred in the first 2 cycles of treatment (up to 28 days post second dose) which was attributed to PF-05082566 alone for Portion A and not related to progressive disease. Hematologic: Grade 4 neutropenia lasting more than (\>)7 days; febrile neutropenia; neutropenic infection; Grade ≥3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia; Grade ≥3 hemolysis. Non-Hematologic: Grade ≥3 toxicities, except those Grade 3 events that responded to treatment (eg, Grade 3 nausea, vomiting, diarrhea responding to standard medical supportive care within 48 hours would not be considered a DLT). Severity of AEs were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE). Each cycle=28 days.
Cycle 1 Day 1 to Cycle 2 Day 29 in Portion A (up to 57 days, each cycle = 28 days)
Number of Participants With DLTs in First 2 Cycles of Portion B
DLT: Any of the following AEs occurred in the first 2 cycles of treatment (up to 28 days post second dose) which was attributed to PF-05082566 in combination with rituximab for Portion B and not related to progressive disease. Hematologic: Grade 4 neutropenia lasting more than (\>)7 days; febrile neutropenia; neutropenic infection; Grade ≥3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia; Grade ≥3 hemolysis. Non-Hematologic: Grade ≥3 toxicities, except those Grade 3 events that responded to treatment (eg, Grade 3 nausea, vomiting, diarrhea responding to standard medical supportive care within 48 hours would not be considered a DLT). Severity of AEs were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE). Each cycle=28 days.
Cycle 1 Day 1 to Cycle 2 Day 29 in Portion B (up to 57 days, each cycle = 28 days)
Secondary Outcomes (41)
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) in Portion A
Up to approximately 2 years
Number of Participants With Treatment-Emergent AEs by Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade in Portion A
Up to approximately 2 years
Number of Participants With Hematology Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion A
Up to approximately 2 years
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion A
Up to approximately 2 years
Number of Participants With Clinically Significant Vital Sign Abnormalities in Portion A
Up to approximately 2 years
- +36 more secondary outcomes
Other Outcomes (3)
Biomarkers Linked With Immunomodulation and Cytokine Release
Days 1, 14, 29 and 57
Exploratory Pharmacodynamic Biomarkers
Days 1 and 21
Patient-Reported Outcomes of PF-05082566 and Rituximab When Given in Combination in Follicular Lymphoma Participants
Up to 2 years
Study Arms (2)
Portion A
EXPERIMENTALPF-05082566 single agent in patients with advanced cancer
Portion B
EXPERIMENTALPF-05082566 in combination with rituximab in patients with Non-Hodgkin's Lymphoma
Interventions
Intravenous, 375 mg/m2, once per week for 4 weeks
Eligibility Criteria
You may qualify if:
- Portion A: Histological or cytological diagnosis of advanced/metastatic solid tumor malignancy or B cell lymphoma, for which no curative therapy is available. Portion A expansion includes patients who have documented disease progression on a checkpoint inhibitor (anti CTLA 4, anti PD1/PD L1 antibodies) per RECIST criteria. Tumor types include metastatic melanoma, renal cell carcinoma (RCC), non-small cell lung cancer (NCSLC) and squamous cell carcinoma of the head and neck (SCCHN). Patients in the dose expansion stage are required to provide archival or baseline (obtained during the screening period) tumor biopsies.
- Portion B: Histological confirmed relapsed or refractory CD20 positive NHL for which no curative therapy is available. Patients enrolled in the expansion cohort must have archival tissue available, sampled within 6 months of study entry. The Expansion cohort includes patients with FL or DLBCL with relapsed or refractory disease.
- Measurable disease with at least one extranodal tumor mass \>1.0 cm in the greatest transverse diameter (GTD) or in the case of malignant lymph nodes \>1.5 cm in the GTD.
- ECOG performance status of ≤ 1.
- Adequate bone marrow function, for Portion A: absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelet count ≥100 x 109/L, hemoglobin \>9.0 g/dL. For Portion B: ANC ≥ 1.0 x 109/L, platelet count ≥ 75 x 109/L, and hemoglobin ≥ 8.0 g/dL. In both cases, patients must be transfusion independent at least 14 days prior to screening.
- Serum creatinine ≤ 2 x ULN or estimated creatinine clearance ≥ 50 ml/min.
- Total serum bilirubin ≤ 1.5 x ULN unless the patient has documented Gilbert syndrome and AST and ALT ≤ 2.5 x ULN.
You may not qualify if:
- Patients with known symptomatic brain metastases requiring steroids.
- Prior allogeneic hematopoietic stem cell transplant.
- Immunosuppressive regimens involving systemic corticosteroids within 14 days before the first dose of study treatment.
- Therapeutic or experimental monoclonal antibodies within 28 day or prior radiation therapy within 14 days of the first dose of study drug.
- Autoimmune disorders and other diseases that compromise or impair the immune system.
- Unstable or serious concurrent medical conditions in the previous 6 months.
- Prior therapy with any anti CD137 monoclonal antibody.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Pfizerlead
Study Sites (42)
City of Hope
Duarte, California, 91010, United States
UC San Diego Moores Cancer Center-Investigational Drug Services
La Jolla, California, 92037-0845, United States
UC San Diego Medical Center-La Jolla (Jacobs Medical Center/Thornton Hospital)
La Jolla, California, 92037, United States
UC San Diego Moores Cancer Center
La Jolla, California, 92093, United States
Research Administration Office: Clinical Research Unit
Los Angeles, California, 90095, United States
Ronald Reagan UCLA Medical Center, Drug Information Center
Los Angeles, California, 90095, United States
UCLA Bowyer Clinic
Los Angeles, California, 90095, United States
UCLA Hematology-Oncology Clinic
Los Angeles, California, 90095, United States
Stanford University Medical Center
Palo Alto, California, 94304, United States
Stanford University Medical Center
Palo Alto, California, 94305, United States
UC San Diego Medical Center - Hillcrest
San Diego, California, 92103, United States
Santa Monica UCLA Hematology & Oncology Clinic
Santa Monica, California, 90404, United States
Stanford University Medical Center
Stanford, California, 94305, United States
Georgetown University Medical Center Department of Pharmacy, Research
Washington D.C., District of Columbia, 20007, United States
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007, United States
Emory University Hospital Midtown
Atlanta, Georgia, 30308, United States
Emory University Hospital
Atlanta, Georgia, 30322, United States
The Emory Clinic, Building A
Atlanta, Georgia, 30322, United States
The Emory Clinic
Atlanta, Georgia, 30322, United States
Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Brigham and Woman's Hospital
Boston, Massachusetts, 02115, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
University of Michigan Health System
Ann Arbor, Michigan, 48109, United States
Siteman Cancer Center - St. Peters
City of Saint Peters, Missouri, 63376, United States
Siteman Cancer Center-West County
Creve Coeur, Missouri, 63141, United States
Barnes-Jewish Hospital
St Louis, Missouri, 63110-1094, United States
Barnes-Jewish Hospital
St Louis, Missouri, 63110, United States
Washington University Infusion Center Pharmacy
St Louis, Missouri, 63110, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Siteman Cancer Center- South County
St Louis, Missouri, 63129, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
The University of Texas - M.D. Anderson Cancer Center
Houston, Texas, 77030, United States
South Texas Accelerated Research Therapeutics, LLC
San Antonio, Texas, 78229, United States
Seattle Cancer Care Alliance
Seattle, Washington, 98109, United States
University of Washington Medical Center
Seattle, Washington, 98195, United States
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000, Australia
Centre d'investigation clinique
Rennes, 35033, France
Az. Ospedaliera-Univer. di Bologna Policlinico S. Orsola Malpighi
Bologna, BO, 40138, Italy
Ospedale San Raffaele di Milano
Milan, MI, 20132, Italy
National Cancer Center Hospital East
Kashiwa, Chiba, 277-8577, Japan
Akita University Hospital
Akita, 010-8543, Japan
The Cancer Institute Hospital of Japanese Foundation for Cancer Research
Tokyo, 135-8550, Japan
Related Publications (2)
Gopal AK, Levy R, Houot R, Patel SP, Popplewell L, Jacobson C, Mu XJ, Deng S, Ching KA, Chen Y, Davis CB, Huang B, Fly KD, Thall A, Woolfson A, Bartlett NL. First-in-Human Study of Utomilumab, a 4-1BB/CD137 Agonist, in Combination with Rituximab in Patients with Follicular and Other CD20+ Non-Hodgkin Lymphomas. Clin Cancer Res. 2020 Jun 1;26(11):2524-2534. doi: 10.1158/1078-0432.CCR-19-2973. Epub 2020 Mar 6.
PMID: 32144134DERIVEDSegal NH, He AR, Doi T, Levy R, Bhatia S, Pishvaian MJ, Cesari R, Chen Y, Davis CB, Huang B, Thall AD, Gopal AK. Phase I Study of Single-Agent Utomilumab (PF-05082566), a 4-1BB/CD137 Agonist, in Patients with Advanced Cancer. Clin Cancer Res. 2018 Apr 15;24(8):1816-1823. doi: 10.1158/1078-0432.CCR-17-1922. Epub 2018 Mar 16.
PMID: 29549159DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Pfizer ClinicalTrials.gov Call Center
- Organization
- Pfizer Inc.
Study Officials
- STUDY DIRECTOR
Pfizer CT.gov Call Center
Pfizer
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 28, 2011
First Posted
March 2, 2011
Study Start
June 21, 2011
Primary Completion
February 20, 2019
Study Completion
February 20, 2019
Last Updated
March 17, 2020
Results First Posted
March 17, 2020
Record last verified: 2020-03
Data Sharing
- IPD Sharing
- Will not share
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.